It seems like everyone wants to give medications through the nose these days. Recently the Pre-Hospital Emergency Care Council of Ireland released the 2014 edition Clinical Practice Guidelines which include intranasal (IN) administration of naloxone for Emergency Medical Technicians. This mode of delivery and medication is now being rolled out to all responder levels in Ireland in order to combat the large number of opioid related deaths in Ireland. IN fentanyl has also recently been added to the analgesia options for Advanced Paramedics in Ireland.

Based on these developments, we began to wonder what other medications could be administered safely through the IN route, resulting in

A study by McDermott & Collins (2012) concluded that the IN route of medication administration is significantly faster, better accepted, and perceived to be safer than using an IV route of administration.

What we found was surprising – many medications can be administered through the IN route – some which you wouldn’t have thought of!

Some key concepts in administering any medication IN are:

Increase the dose

Decrease the volume

Use both nostrils

Use a MAD

Below you will find medications commonly used in the prehospital setting that have been administered successfully through the IN route, along with references to abstracts and articles where available. There are other medications that can be given IN, but they aren’t in most EMT or Paramedic formularies worldwide, so we’ve left them out.

If you’d like to read more than you ever thought possible on IN medication administration, Dr. Tim Wolfe, one of the original designers of the Mucosal Atomiser Device (MAD) used in IN administration runs a great website detailing further medications and resources regarding IN medication administration. Find it at http://www.intranasal.net

If you have experience delivering any of these medications through the IN route we’d love to hear your thoughts – leave a comment below! Usual obvious disclaimers apply to this post – always operate to your scope of practice and local protocols etc.

Atropine

Intranasal atropine use has been reported in the treatment of organophosphate poisoning (OP) in one animal study (Pravin et al 2001), and is commonly used in humans for treating rhinorrhea and postnasal drip (Baroody et al 1996). One paper from Ozyurt et al (2003) details the successful use of aerosolised atropine administered through the IN route in the management of three patients with OP poisoning – however, all of these patients also received IV doses of atropine. No literature exists as yet on the use of IN atropine in human subjects with symptomatic bradycardia.

Fentanyl

IN fentanyl has been shown to have a rapid onset and efficiency similar to that of IV, is easier to administer in children who may be in severe pain, and is quicker to administer than establishing an IV and administering an IV analgesic. Borland et al. (2002 & 2007) found that IN fentanyl was better than morphine for pain relief in children, however Rickard (2007) found no difference between the two medications. A systematic review by Mudd in 2011 concluded that INF is a safe and effective method of pain management for children in a variety of clinical settings. Gausche et al (2014) also recommend IN fentanyl in their Evidence-based Guideline for prehospital analgesia in trauma. However, Hansen & Dahl (2013) argue that there is limited evidence for IN fentanyl in the prehospital setting and that further research is required, a view that was shared by Dale et al in 2002.

Dale O1, Hjortkjaer R, Kharasch ED. Nasal administration of opioids for pain management in adults. Acta Anaesthesiol Scand. 2002 Aug;46(7):759-70. PMID: 12139528.
Nasal administration of opioids may be an alternative route to intravenous, subcutaneous, oral transmucosal, oral or rectal administration in some patients. Key features may be self-administration, combined with rapid onset of action. The aim of this paper is to evaluate the present base of knowledg [...]

Flumazenil

The evidence is sparse for IN administration of flumazenil. Heard et al (2009) describe a case of over-sedation of a 3 year old child with IN sulfentanil and midazolam which was successfully reversed by IN administration of naloxone and flumazenil. A study carried out by Sheepers et al in 2000 showed that plasma concentrations of flumazenil were similar between IN and IV administration, concluding that this route of administration (IN) may be useful when the intravenous route is not readily available.

Glucagon

Intranasal glucagon has been shown to be effective in treating hypoglycaemia in a number of case reports and studies. Sibley et al (2013) published a case report detailing the successful administration of IN glucagon to a female hypoglycaemic patient in the prehospital setting. Pontiroli et al., as far back as 1989 suggested that IN glucagon could be a potential emergency solution to hypoglycaemic episodes. Stenninger & Aman (1993) found that IN glucagon resulted in a slower plasma glucose rise, but was associated with less side-effects. Rosenfalck found between treatment with 2mg IN and 1mg IM that IN results in a lower overall plasma glucose level 40 minutes after administration, and that 80% of the patients treated with IN glucagon had some localised side effects such as rhinitis. There is a lack of recent, robust clinical trials in favour of IN glucagon, and this is an area that warrants further research.

Sibley T1, Jacobsen R, Salomone J. Successful administration of intranasal glucagon in the out-of-hospital environment. Prehosp Emerg Care. 2013 Jan-Mar;17(1):98-102. PMID: 22971130.
We present a case of successful prehospital treatment of hypoglycemia with intranasal (IN) glucagon. Episodes of hypoglycemia can be of varying severity and often requires quick reversal to prevent alteration in mental status or hypoglycemic coma. Glucagon has been shown to be as effective as glucos [...]

Ketamine

IN ketamine can be used for sedation and analgesia purposes. However, doses need to be increased (as they do with most medications if administering via the IN route). Tsze et al (2012) found the a dose of 9mg/kg of IN ketamine produced successful sedation (when compared with 3mg/kg and 6mg/kg doses). Johanssen et al (2013) describe a series of nine cases treated with IN ketamine in which all patients achieved analgesia with little side-effects, with their conclusion being that IN ketamine may reduce the time spent on the scene of the accident and most likely reduces the need to expose the patient to the environment in especially challenging cases of prehospital analgesia. Reid et al (2013) also present a case report of successful analgesia with IN ketamine in a paediatric burn victim. Yeaman et al (2013) concluded that an average dose of 1.0 mg/kg IN ketamine provided adequate analgesia by 30 min for most of the 28 paediatric patients in the study with isolated limb injuries, and in a further study of adult patients in 2014 found that 56% of the 72 patients studied had adequate pain relief from doses of approximately 1 mg/kg.

Johansson J1, Sjöberg J, Nordgren M, Sandström E, Sjöberg F, Zetterström H. Prehospital analgesia using nasal administration of S-ketamine--a case series. Scand J Trauma Resusc Emerg Med. 2013 May 14;21:38. PMID: 23672762.
Pain is a problem that often has to be addressed in the prehospital setting. The delivery of analgesia may sometimes prove challenging due to problems establishing intravenous access or a harsh winter environment. To solve the problem of intravenous access, intranasal administration of drugs is used [...]

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Reid C1, Hatton R, Middleton P. Case report: prehospital use of intranasal ketamine for paediatric burn injury. Emerg Med J. 2011 Apr;28(4):328-9. PMID: 21292791.
In this study, the administration of an intravenous ketamine formulation to the nasal mucosa of a paediatric burn victim is described in the prehospital environment. Effective analgesia was achieved without the need for vascular or osseous access. Intranasal ketamine has been previously described fo [...]

Lorazepam

In 2011, Arya et al published a very interesting paper which showed that IN lorazepam was as effective as IV lorazepam for controlling seizures – and was administered much quicker in the population studied. A BestBET topic by Allan & Cullen (2013) concluded that intranasal lorazepam appears to be an acceptable intervention for the termination of seizures, demonstrating both efficacy and safety.

Metoclopramide

Metoclopramide is an effective anti-emetic agent, and has been successfully administered through the IN route by Ormrod & Goa (1999), who found that an 80mg IN dose reduced the frequency of acute vomiting in chemotherapy patients. However, Wagner at al (1996) in a double-blind, placebo-controlled evaluation of intranasal metoclopramide in the prevention of postoperative nausea and vomiting (PONV) found that a 20mg dose was ineffective in preventing the occurrence of PONV – they do however recognise these results may be due to an inadequate dose.

Ormrod D1, Goa KL. Intranasal metoclopramide. Drugs. 1999 Aug;58(2):315-22; discussion 323-4. PMID: 10473023.
Intranasal metoclopramide is a new formulation of an established and effective antiemetic drug. Absorption after intranasal administration was lower than after oral or intravenous administration; otherwise the pharmacodynamic and pharmacokinetic profiles of the intranasal and parenteral formulations [...]

Midazolam

Rainbow et al. (2002) found that intranasal midazolam can control seizures as effectively as diazepam in the prehospital setting. Intranasal midazolam can also result in a comparable time to cessation of seizures to that of intravenous diazepam (Lahat et al., 2000). Wolfe & Macfarlane (2006) found that intranasal midazolam can provide better seizure control than PR diazepam, and is easier for paramedics to administer to a patient who is actively seizing. A number of authors (Scott et al, 1999; Wilson et al., 2004; Humphries & Eiland, 2013) also found that patients and caregivers found intranasal midazolam to be more socially acceptable than per rectum administration of diazepam, as well as re-confirming the view it was more convenient for paramedics to access the intranasal route than the per rectum route. Fisgin et al (2002) compared intranasal midazolam to rectal diazepam and found midazolam was more effective than diazepam. A prehospital study by Holsti et al (2007), found that IN midazolam showed better prehospital seizure control, less need for need for emergent intubation and less need for hospital admission in the intranasal midazolam group compared with the rectal diazepam group. Bhattacharyya (2006) in a randomised study of 46 children (188 seizure episodes) concludes intranasal midazolam is preferable to rectal diazepam in the treatment of acute seizures in children.

Humphries LK1, Eiland LS. Treatment of acute seizures: is intranasal midazolam a viable option? J Pediatr Pharmacol Ther. 2013 Apr;18(2):79-87. PMID: 23798902.
Seizures in the pediatric population commonly occur, and when proper rescue medication is not administered quickly, the risk of neurologic compromise emerges. For many years, rectal diazepam has been the standard of care, but recent interest in a more cost-effective, safe alternative has led to the [...]

Wolfe TR1, Macfarlane TC. Intranasal midazolam therapy for pediatric status epilepticus. Am J Emerg Med. 2006 May;24(3):343-6. PMID: 16635708.
Prolonged seizure activity in a child is a frightening experience for families as well as care providers. Because duration of seizure activity impacts morbidity and mortality, effective methods for seizure control should be instituted as soon as possible, preferably at home. Unfortunately, parentera [...]

Wilson MT1, Macleod S, O'Regan ME. Nasal/buccal midazolam use in the community. Arch Dis Child. 2004 Jan;89(1):50-1. PMID: 14709505.
A telephone survey was carried out to evaluate the effectiveness and convenience of nasal/buccal midazolam in terminating prolonged seizures in the community. A total of 33/40 (83%) families who had used it found it effective and easy to use; 20/24 (83%) preferred using midazolam to rectal diazepam. [...]

Morphine

Christensen et al (2008) studied 225 patients post dental surgery with randomisation to either IN morphine, IV morphine, PO morphine or placebo, and concluded that IN morphine offers a noninvasive alternative to IV morphine for postoperative analgesia. Stoker et al (2008) found that IN morphine-chitosan solution provided sustained analgesia in postsurgical patients and thus may offer a safe and less invasive alternative to IV morphine.

Naloxone

Naloxone is routinely administered in the prehospital setting through IV and IM routes, but many studies have shown its efficacy when administered IN. Kerr et al (2009) in a study of 172 patients in the pre-hospital setting found intranasal naloxone reversed heroin overdose successfully in 82% of patients, with a similar time of response to IM naloxone. Barton et al (2005) also came to similar conclusions. Kelly (2005) found that IN naloxone was effective at treating opioid induced respiratory depression, but not as effective as IM. Bystanders with no medical training used naloxone to successfully reverse opioid overdose in 74 times in a take-home naloxone study by Doe-Simkins et al (2009). A BestBET by Ahston & Hassan (2006) concluded it is likely that intranasal naloxone is a safe and effective first line prehospital intervention in reversing the effects of an opioid overdose and helping to reduce the risk of needle stick injury, but that a large, well conducted trial into it’s usage is required.

Ashton H1, Hassan Z. Best evidence topic report. Intranasal naloxone in suspected opioid overdose. Emerg Med J. 2006 Mar;23(3):221-3. PMID: 16498165.
A short cut review was carried out to establish whether intransasal naloxone is effective in suspected opiate overdose. 596 papers were screened, of which eight presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type [...]

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Salbutamol

Weksler et al (1999) describe three cases where salbutamol was successfully administered through the IN route after the patients were found to be unresponsive to conventional therapy. The only other available literature is an animal study by Hussain et al (2004) which showed albuterol (salbutamol) to be equally effective when administered either intranasally or intratracheally.

Weksler N1, Brill S, Tarnapolski A, Gurman GM. Intranasal salbutamol instillation in asthma attack. Am J Emerg Med. 1999 Nov;17(7):686-8. PMID: 10597090.
Beta-two sympathomimetic drugs are the treatment of choice for asthmatic attack. Their main effect is to dilate the bronchi by a direct action on beta-two adrenoreceptors on the smooth muscle, and also by mediator release inhibition from mast cells. Salbutamol is widely used in the treatment of bron [...]

Hussain AA1, Dakkuri A, Lai YL, Traboulsi A, Hussain MA. Nasal administration of albuterol: an alternative route of delivery. J Pharm Pharmacol. 2004 Oct;56(10):1211-5. PMID: 15482634.
The use of metered-dose inhalers for the delivery of albuterol, a beta2-selective adrenergic agonist, is associated with drawbacks, especially in children and the elderly. This investigation was designed to assess the effectiveness of albuterol delivered intranasally and to compare this delivery rou [...]

Tranexamic Acid

While not technically intranasal in the sense we have been discussing, the new kid on the block for many EMS providers, TXA applied to a pledget was better than anterior nasal packing in the initial treatment of idiopathic anterior epistaxis in a study by Zahed et al in 2013. There’s not much evidence to support it’s widespread use though, further studies are needed.

Additional Resources & References

Collopy KT1, Snyder SR. Intranasal drug administration: an innovative approach to traditional care. EMS World. 2011 May;40(5):45-50. PMID: 21650113.
Intranasal drug administration is safe and effective and has many applications to prehospital providers of all levels. Administered drugs do take longer to take effect than drugs administered intravenously; however, the time saved by not needing to establish an i.v. offsets this difference. When eva [...]

Del Pizzo J1, Callahan JM. Intranasal medications in pediatric emergency medicine. Pediatr Emerg Care. 2014 Jul;30(7):496-501; quiz 502-4. PMID: 24987995.
Intranasal medication administration in the emergency care of children has been reported for at least 20 years and is gaining popularity because of ease of administration, rapid onset of action, and relatively little pain to the patient. The ability to avoid a needle stick is often attractive to pra [...]

Dr. Tim Wolfe, one of the original designers of the Mucosal Atomiser Device (MAD) used in IN administration runs a great website detailing further medications and resources regarding IN medication administration. Find it at http://www.intranasal.net

Alan is a critical care paramedic, paramedic educator and prehospital researcher, currently working around the world as an educator and researcher. He has previously worked and studied across Europe, North America and the Middle East. He holds a Graduate Certificate in Intensive Care Paramedic Studies, and an MSc in Critical Care. His main interests are in care of the elderly, end-of-life care, patient safety, professionalism (including role and identity), and paramedic education.